crossing96/oncoscreening huggingface dataset:
Effects of radiation and lifestyle factors on risks of urothelial carcinoma in the Life Span Study of atomic bomb survivors.	Among the Life Span Study (LSS) of Atomic-bomb survivors, recent estimates showed that unspecified bladder cancer had high radiation sensitivity with a notably high female-to-male excess relative risk (ERR) per radiation dose ratio and were the only sites for which the ERR did not decrease with attained age. These findings, however, did not consider lifestyle factors, which could potentially confound or modify the risk estimates. This study estimated the radiation risks of the most prevalent subtype of urinary tract cancer, urothelial carcinoma, while accounting for smoking, consumption of fruit, vegetables, alcohol and level of education (a surrogate for socioeconomic status). Eligible study subjects included 105,402 (males = 42,890) LSS members who were cancer-free in 1958 and had estimated radiation doses. Members were censored due to loss of follow-up, incident cancer of another type, death, or the end of calendar year 2001. Surveys (by mail or clinical interview) gathered lifestyle data periodically for 1963-1991. There were 63,827 participants in one or more survey. Five hundred seventy-three incident urothelial carcinoma cases occurred, of which 364 occurred after lifestyle information was available. Analyses were performed using Poisson regression methods. The excess relative risk per weighted gray unit (the gamma component plus 10 times the neutron component, Gy(w)) was 1.00 (95% CI: 0.43-1.78) but the risks were not dependent upon age at exposure or attained age. Lifestyle factors other than smoking were not associated with urothelial carcinoma risk. Neither the magnitude of the radiation ERR estimate (1.00 compared to 0.96), nor the female-to-male (F:M) ERR/Gy(w) ratio (3.2 compared to 3.4) were greatly changed after accounting for all lifestyle factors. A multiplicative model of gender-specific radiation and smoking effects was the most revealing though there was no evidence of significant departures from either the additive or multiplicative joint effect models. Among the LSS cohort members with doses greater than 0.005 Gy(w) (average dose 0.21 Gy(w)), the attributable fraction of urothelial carcinoma due to radiation was 7.1% in males and 19.7% in females. Among current smokers, the attributable fraction of urothelial carcinoma due to smoking was 61% in males and 52% in females. Relative risk estimates of smoking risk were approximately two for smokers compared to nonsmokers. After adjustment for lifestyle factors, gender-specific radiation risks and the F:M ERR/Gy(w), the ratios of excess urothelial carcinoma risk were similar to the estimates without adjusting for lifestyle factors. Smoking was the primary factor responsible for excess urothelial carcinoma in this cohort. These findings led us to conclude that the radiation risk estimates of urothelial carcinoma do not appear to be strongly confounded or modified by smoking, consumption of alcohol, fruits, or vegetables, or level of education.	bladder
Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic marker in patients with urothelial carcinoma of the bladder.	BACKGROUND: Urothelial carcinoma of the bladder is characterised by very high recurrence rate, followed up by cystoscopy which being invasive technique makes the need for non-invasive markers important for Transitional Cell Carcinoma (TCC) detection. CD147 is a transmembrane protein highly expressed in tumour cells which aids in tumour invasion and growth. BIGH3, an Extracellular matrix protein (ECM) which interacts with various ECM component in different tissue system and Stathmin(STMN1) is cytosolic microtubule destabilising protein also called as Oncoprotein18 due to its role in tumour promotion. So far the expression of BIGH3 and STMN1 remains undetermined in cancer subjects including TCC. We therefore studied the levels and molecular expression of these molecules in TCC patients, to evaluate their usefulness as diagnostic markers. METHODS: Thirty consecutive TCC patients and two sets of control- 15 Benign prostatic hyperplasia (BPH) patient and 15 healthy were taken. Serum and urine levels of these molecules were estimated by ELISA and relative mRNA expression by Q-PCR from tumour and normal urothelium. Post-Hoc analysis and ROC curve were determined to evaluate the significance and sensitivity and specificity. RESULTS: The mean concentrations of these molecules were found to be significantly increased (p<0.001) in the serum and urine of TCC patients, with varying significance in each grade for different molecules. The urinary levels of CD147 (67 pg/ml) and serum STMN1 concentration (1.38 ng/ml) showed a specific increase as compared to the controls, while BIGH3 was elevated in both serum and urine samples. Molecular (mRNA) expression was elevated in the high grade (Muscle Invasive) stage of the disease for all the molecules, with a significant 3-fold increase that correlated with disease severity being observed for STMN1. ROC analysis gave optimal combination of sensitivity and specificity for diagnosis of the disease in urine and serum sample for STMN1. CONCLUSION: Of CD147, BIGH3 and STMN1, significant results were obtained for STMN1 and it could serve as the best possible diagnostic marker for TCC detection in future.	bladder
Urodynamic characteristics of the modified orthotopic ileal neobladder.	BACKGROUND/AIM: Radical cystectomy is the method of choice in management of muscle invasive, organ-confined tumors of the bladder (T2-T4, N0-Nx). The most frequent continent orthotopic urinary diversion after radical cystectomy is the ileal neobladder. A modified technique consists of using a shorter segment of the terminal ileum than the standard technique, around 30 cm. The aim of this study was to determine the urodynamic characteristics of the orthotopic ileal neobladder created by a modified technique. METHODS: In this prospective clinical study we analyzed the urodynamic parameters of 24 patients who had underwent radical cystectomy with orthotopic urinary diversion by ileal neobladder created using a modified technique. In all the patients we performed invasive and noninvasive urodynamic investigations 12 months after the operation. The urethral pressure profile parameters analyzed were maximal urethral pressure, maximal urethral closure pressure and the functional urethral profile length. RESULTS: The average age of the patients was 63 (49-73) years, 90% were males and 10% were females. The median length of the shorter segment of the terminal ileum was 28 (range 22-35) cm. Prior to enterocystometry and uroflowmetry postvoid residual (PVR) urine was measured by a urethral catheter. The median PVR was 16.7 (0-140) mL. The median enterocystometric capacity was 396 (range 372-532) mL. The median end filling pouch pressure was 27.6 (range 20-70) cmH2O. The median maximal flow of urine was 22.1 (range 9.7-39.5) mL/s and the average flow of urine was 9.61 (range 3.6-17.6) mL/s. Flow time in the analyzed group was 47.5 (range 22-119) s. The median maximal urethral pressure was 54 (range 12-101) cmH2O, maximal urethral closure pressure 36.6 (range 6-91) cmH2O. Functional urethral profile length was 14.9 (range 4-37) mm. CONCLUSION: An ileal orthotopic pouch created by a modified technique using a shorter segment of the terminal ileum after 12 months presents with urodynamic characteristics similar to the native bladder.	bladder
Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis.	Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer.	bladder
Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.	Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.	bladder
Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.	BACKGROUND: Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway. METHODS: Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy. RESULTS: All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively. CONCLUSIONS: AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.	bladder
Plasma thymosin-α1 level as a potential biomarker in urothelial and renal cell carcinoma.	OBJECTIVES: To determine the plasma levels of thymosin-α1 (TA1) and prothymosin-α (PTMA) proteins in renal cell carcinoma (RCC) or urothelial carcinoma (UC) patients, and explore the potential of these 2 molecules as biomarkers. MATERIALS AND METHODS: Blood samples were taken from 50 consecutive patients with RCC, 97 with UC, and 55 with benign urologic diseases before surgery. Their clinical characteristics were obtained from medical record review. Plasma TA1 and PTMA levels were measured using enzyme-linked immunosorbent assay and their correlation with tumor grade, pathologic stage, and survival were explored. RESULTS: Plasma TA1 levels were significantly lower in RCC patients than in UC or benign patients, particularly in UC of the renal pelvis patients (P < 0.0001). Plasma PTMA levels were also significantly lower in UC patients compared with RCC patients and benign patients (P < 0.05). Plasma TA1 levels inversely correlated with pathologic stage both in bladder cancer and RCC patients (P = 0.03 and 0.02, respectively). Both plasma TA1 and PTMA did not correlate with tumor grade. Plasma TA1 was a prognostic indicator for progression-free and disease-specific overall survival in bladder cancer patients (P = 0.008 and 0.04, respectively). CONCLUSIONS: Plasma TA1 level may be a biomarker for differentiating between UC and RCC. It may also be a prognostic factor for disease progression and disease-specific survival in bladder cancer patients. These findings warrant more studies for validation.	bladder
DNMT1: an emerging target in the treatment of invasive urinary bladder cancer.	"OBJECTIVES: More than 14,000 people die from invasive urothelial carcinoma (iUC) of the urinary bladder each year in the USA, and more effective therapies are needed. Naturally occurring canine iUC very closely resembles the disease in humans and serves as a highly relevant translational model for novel therapy of human iUC. Work was undertaken to identify new targets for anticancer therapy in dogs with the goal of translating successful therapeutic strategies into humans with iUC. MATERIALS AND METHODS: Microarray expression analyses were conducted on mRNA extracted from canine normal bladder (n = 4) and iUC tissues (n = 4) using Genome Array 1.0 and analyzed by GeneSpring GX 11, with the stringency of P < 0.02 and a ≥ 2-fold change. The genes thus identified were further analyzed for functional and pathway analysis using Protein ANalysis THrough Evolutionary Relationships (PANTHER) Classification System. In selecting genes for further study, consideration was given for evidence of a role of the gene in human iUC. From these analyses, DNA methyltransferase 1 (DNMT1) was selected for further study. Immunohistochemistry (IHC) of canine normal bladder and iUC tissues was performed to confirm the microarray expression analyses. The effects of targeting DNMT1 in vitro was assessed through MTT assay and Western blot of canine iUC cells treated with 5-azacitidine (5-azaC) and trichostatin A (TSA). RESULTS: DNMT1 was expressed in 0 of 6 normal canine bladder samples and in 10 of 22 (45%) canine iUC samples. The proliferation of canine iUC cells was inhibited by 5-azaC (at concentrations ≥ 5 μm) and by TSA (at concentrations ≥ 0.1 μm). Western blot results were supportive of DNMT1-related effects having a role in the antiproliferative activity. CONCLUSIONS: Microarray expression analyses on canine tissues identified DNMT1 as a potentially ""targetable"" gene. Expression of DNMT1 in canine iUC was confirmed by IHC, and in vitro studies confirmed that drugs that inhibit DNMT1 have antiproliferative effects. These findings are similar to those recently reported in human iUC and are also in line with results of a preclinical (prehuman) trial of 5-azaC in dogs with naturally occurring iUC. DNMT1 has excellent potential as a target for iUC therapy in humans."	bladder
Androgen receptor signaling regulates cell growth and vulnerability to doxorubicin in bladder cancer.	PURPOSE: There are several reports of androgen receptor in bladder cancer cases but androgen receptor expression and the function of androgen/androgen receptor signaling in bladder cancer remain unclear. We investigated androgen receptor expression and the role of androgen/androgen receptor signaling in bladder cancer. MATERIALS AND METHODS: We evaluated AR mRNA expression in bladder cancer tissue by quantitative real-time polymerase chain reaction. The role of androgen receptor in cell growth and drug sensitivity was also evaluated in vitro and in vivo in several bladder cancer cell lines. RESULTS: AR mRNA expression inversely correlated with bladder cancer grade, stage and spread. Of several bladder cancer cell lines UMUC3 and MBT-2 markedly expressed androgen receptor transcript and protein. In each cell line androgen/androgen receptor signaling blockade using androgen deprivation, blockade knockdown and antiandrogen agents decreased cell growth, colony formation and cell viability. Androgen receptor expression was implicated in doxorubicin resistance. Inversely androgen receptor deprivation and knockdown made UMUC3 cells sensitive to doxorubicin. Finally, castration slightly suppressed UMUC3 tumor growth in vivo, although this did not attain statistical significance. CONCLUSIONS: AR transcript expression inversely correlates with bladder cancer clinicopathological characteristics. Androgen/androgen receptor signaling has an important role in the growth and vulnerability to doxorubicin of bladder cancer cells that express androgen receptor. Androgen/androgen receptor signaling might be a possible prophylactic and therapeutic target for bladder cancer that shows androgen receptor expression.	bladder
Exstrophy polyp is a unique pathology entity.	Classic bladder exstrophy is a rare congenital malformation occurring with an incidence of about 1 in 50 000 live births. Polypoid lesions frequently arise in the exstrophic bladder template; this has been well described in the pediatric urological literature. These lesions, however, are not as familiar to pathologists and oftentimes constitute diagnostic challenges. Careful observation revealed that these polyps are unique in their histopathologic appearance, with deep penetrating nests of urothelium or cysts and surrounding concentric fibrosis. Combining the unique clinical setting, a separate pathologic and diagnostic entity should be initiated for this type of polyp; we propose the term 'bladder exstrophy polyp' or simply an 'exstrophy polyp.'	bladder
The role of the androgen receptor in the development and progression of bladder cancer.	Men are at a higher risk of developing bladder cancer than women. Since bladder cancer cell lines and tissues were found to express the androgen receptor, efforts have been made to inspect whether androgen-mediated androgen receptor signals are implicated in bladder carcinogenesis as well as cancer progression. Mounting evidence supports the view that bladder cancer is a member of the endocrine-related tumors and may clearly explain the gender-specific difference in the incidence. However, the underlying mechanisms of how androgen receptor signals regulate bladder cancer growth are still far from fully characterized. Moreover, it remains controversial whether the androgen receptor pathway always plays a dominant role in bladder cancer progression. In this review, we summarize the available data on the involvement of androgen receptor signaling in bladder cancer. In particular, current evidence demonstrating the stimulatory effects of androgens on tumor progression or, more convincingly, tumorigenesis via the androgen receptor pathway may offer great potential for androgen deprivation as a therapeutic or chemopreventive option in patients with bladder cancer.	bladder
Pelvic urothelial carcinoma with nested pattern of growth and an uncommon clinical presentation: a case report.	BACKGROUND: Nested variant of urothelial carcinoma (NVUC) is a rare and often unrecognized urothelial neoplasia. Diagnosis is based on morphology only, and no immunohistochemical or cytogenetic differences from usual high-grade urothelial carcinomas have been reported. CASE: We describe the case of a 49-year-old woman affected by hepatitis C virus presented with fever, discomfort, urgency, and hypertension. Computed tomography showed a sclerosing inflammatory process involving the connective and adipose tissue of the renal sinus. In the absence of renal or pelvic masses an underlying malignancy was excluded and renal abscess or tuberculosis was suspected. Accordingly, nephrectomy and proximal ureterectomy was performed. Grossly, calices, renal pelvis, and pyeloureteral junction appeared modestly dilated with whitish, thickened, and uneven mucosa. Microscopically, the subepithelial connective tissue, the fibromuscular layer, and the renal sinus fat were diffusely infiltrated by small nests of medium to large urothelial cells (p63 positive) with abundant eosinophylic cytoplasm and slightly atypical nuclei. CONCLUSION: On the basis of morphologic and immunohistochemical features, a diagnosis of NVUC was made. After surgery, the patient recovered from hypertension. Pelvic and upper urothelial tract NVUCs are uncommon, and to the best of our knowledge, this is the second case of NVUC with renal involvement.	bladder
Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.	Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001), and loss of FOXA1 is associated with high histologic grade (p<0.001). Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC) exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes of MIBC and urothelial cell proliferation, and suggest an important role for FOXA1 in the malignant phenotype of MIBC.	bladder